Process for production of dimers of aromatic monohydroxyl compounds

ABSTRACT

The present invention provides a method for preparing dimer of a monohydroxy aromatic compound. In the method of the present invention, oxidative coupling reaction of a monohydroxy aromatic compound represented by formula [I]:  
     Ar—OH   [I] 
     wherein Ar represents an optionally substituted aromatic group is carried out in a nitrogen containing polar solvent in the presence of a copper salt. By the method of the instant invention, dimer of the monohydroxy aromatic compound can be obtained in high yield.

TECHNICAL FIELD

[0001] The present invention relates to a method for preparing dimer ofa monohydroxy aromatic compound

BACKGROUND ART

[0002] 1,1′-bi-2-naphthol, a compound obtainable by dimerization ofβ-naphthol or its derivative, is useful for preparing an antisepticcompound or an asymmetric synthesis catalyst.

[0003] In addition, dimers of 2-hydroxynaphthalene-3-carboxylic acid andof 2-hydroxynaphthalene-6-caboxylic acid are useful as toning agents.

[0004] U.S. Pat No. 3,278,610 discloses a method for preparing the abovedescribed dimers, which comprises dimerizing β-naphthol in a solventsuch as benzene in the presence of copper chloride, amine and oxygen.

[0005] J. Org. Chem. 1999, 64, 2264-2271 discloses a method fordimerizing β-naphthol or the like, which comprises oxidative coupling ofβ-naphthol, methyl 2-hydroxynaphthalene-3-carboxylate or the like in thepresence of copper(I) chloride-tetramethylethylenediamine complex indichloromethane, wherein copper(I) chloride and tetramethylethylenediamine are combined before the coupling reaction.

DISCLOSURE OF THE INVENTION

[0006] Conventional methods for preparing binaphthol derivatives requirea solvent, such as benzene or dichloromethane, to dissolve β-naphthol orthe like therein to facilitate the coupling reaction, and the solventcauses high cost. Further, the method of J. Org. Chem. 1999, 64,2264-2271 is complex because the method comprises the extra step ofcombining copper(I) chloride and tetramethyl ethylene diamine prior tothe coupling reaction.

[0007] One object of the present invention is to solve the aboveproblems and to provide a method for preparing a binaphthol derivativein high yield with low cost.

[0008] Another object of the present invention is to provide a methoduseful for dimerizing not only soluble compounds, such as β-naphthol andphenol, but also hardly soluble monohydroxy aromatic compound, such asmonohydroxy naphthalene dicarboxylic acid derivative.

[0009] The instant inventors intensively studied with respect todimerization of monohydroxy aromatic compounds and have found thatdesired dimer of a monohydroxy aromatic compound can be obtained in highyield by carrying out the oxidative coupling reaction of said compoundin a nitrogen containing polar solvent in the presence of a copper saltas a catalyst, and completed the invention.

[0010] Accordingly, the present invention provides a method forpreparing dimer of a monohydroxy aromatic compound represented byformula [I]:

Ar—OH   [I]

[0011] wherein Ar represents an optionally substituted aromatic group,characterized in that carrying out oxidative coupling reaction of saidcompound in a nitrogen containing polar solvent in the presence of acopper salt.

[0012] The reason why the present method can provide the dimer in highyield may be that the copper salt reacts with the hydroxy group of theformula [1] monohydroxy aromatic compound, the nitrogen containing polarsolvent and oxygen to provide a complex having oxidizing ability, andthe complex affects as a catalyst to promote the oxidative couplingreaction.

[0013] Examples of copper salts used in the present invention mayinclude copper(I) chloride, copper(II) chloride, copper (I) bromide,copper(II) bromide, copper(I) iodide, copper(II) acetate and copper (II)formate. Copper(I) chloride is most preferable among them, since itscatalytic ability is recovered by oxygen during the reaction andaccordingly the amount of the copper salt used in the reaction can bereduced.

[0014] When copper(I) chloride is used, it is recommendable to supplyair or oxygen actively into the reaction.

[0015] The amount of copper salt used in the reaction may be 0.5-100mole, preferably, 5-10 mole per 100 mole of the formula [1] monohydroxyaromatic compound.

[0016] When the amount of copper salt is less than 0.5 mole per 100 moleof the monohydroxy aromatic compound, the reaction speed may become veryslow, and when the amount is more than 100 mole, an unfavorable sidereaction may occur.

[0017] In the method of the instant invention, the nitrogen containingpolar solvent plays roles as a reaction medium to facilitate thereaction and also as a ligand which forms a complex having an oxidativeability with the copper salt. Preferable nitrogen containing polarsolvents may be those represented by formulae [III] and [IV].

[0018] wherein R₁, R₂, R₃ and R₄ may be same or different and each isindependently selected from the group consisting of formyl, alkyl,alkenyl, acyl and optionally substituted phenyl groups.

[0019] Examples of R₁, R₂, R₃ and R₄ may include formyl, alkyl of 1-6carbon atoms such as methyl, ethyl, propyl and hexyl; alkenyl of 2-6carbon atoms such as vinyl, allyl and pentenyl, acyl of 1-6 carbon atomssuch as acetyl group and optionally substituted phenyl.

[0020] Examples of the substituent may include halogen atom, halogenatedlower alkyl, lower alkyl, lower alkoxy such as methoxy, phenyl,naphthyl, phenoxy, furyl, amino, toluidylamino, triazylamino,pyrimidylamino, benzoylamino, hydroxy, esterified carboxyl group such asalkoxycarbonyl and phenoxycarbonyl groups, amidated carboxyl group suchas phenylcarbamoyl group, alkylaminosulfonyl group and alkenyl group of2-6 carbon atoms which may contain aryl group.

[0021] When the substituent contains an aromatic ring, the compound mayfurther have one or more substituents such as halogen atom, lower alkyl,lower alkoxy and phenyl on said aromatic ring.

[0022] Examples of the solvent represented by formula [III] may includeN,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylacetaminde,N,N-dimethylpropyoamide, N-methylacetanilide, N,N-dimethylaniline andN,N-dimethylanisidine. Examples of solvent represented by formula [IV]may contain tetramethylurea and tetraethylurea.

[0023] Preferable nitrogen containing polar solvent may includeN,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone,morpholine, N-methylmorpholine, N,N-diethylacetamide,N,N-dimethylpropyoamide, tetramethylurea, tetraethylurea,N-methylacetanilide, N,N-dimethylaniline, N,N-dimethylanisidine,pyridine, and 2-methylpyridine. Especially, N,N-dimethylformamide,N,N-dimethylacetaminde and N-methyl-2-pyrrolidone are preferable sincethey can dissolve the hardly soluble ester or amide derivative of2-hydroxynaphthalene-3,6-dicarboxylic acid well.

[0024] An amount of the nitrogen containing polar solvent enough todissolve the monohydroxyaromatic compound of formula [I] may be used forthe reaction. Typically, the amount may be 5-50, preferably 5-20, morepreferably 5-10, fold by weight of the formula [I] monohydroxy aromaticcompound.

[0025] The method of the present invention may be carried out asfollows.

[0026] Firstly, the monohydroxyaromatic compound of formula [I] isdissolved or dispersed in a nitrogen containing polar solvent at roomtemperature. A copper salt is added thereto and the obtained reactionmixture is then heated to 40-120° C., preferably 60-80° C. under apressurized or a normal pressure condition to undergo the oxidativecoupling reaction so that dimer of the monohydroxyaromatic compound isobtained.

[0027] The duration of the oxidative coupling reaction may be determineddepending on the amount of the catalyst and the reaction temperature.Generally, the reaction time may be 1-48 hours. The completion of thereaction may be confirmed by disappearance of the starting material inthe reaction mixture, which can be monitored with HPLC or the like.

[0028] After the oxidative coupling reaction is completed, the reactionsolution or that admixed with water may be filtrated, washed and, ifdesired, recrystalized to give crystalline dimeric monohydroxy aromaticcompound.

[0029] The monohydroxy aromatic compound which can be dimerizedaccording to the instant invention is a compound represented by formula[I]:

Ar—OH   [I]

[0030] wherein Ar is an optionally substituted aromatic group. Examplesof the aromatic groups may include phenyl, naphthyl, anthryl andpyrenyl.

[0031] Examples of the substituents may include halogen atom,halogenated lower alkyl, lower alkyl, lower alkoxy such as methoxy,phenyl, naphthyl, phenoxy, furyl, amino, toluidylamino, triadilamino,pyrimidylamino, benzoylamino, esterified carboxyl such as alkoxycabonyland phenoxycarbonyl, amidized carboxyl such as phenylcarbamoyl,alkylaminosulfonyl, alkenyl of 2-6 carbon atoms which may include anaryl group.

[0032] When the substituent contains an aromatic ring, the compound mayfurther have one or more substituents such as halogen atom, lower alkyl,lower alkoxy and phenyl groups on said aromatic ring.

[0033] In the present specification and claims, “lower” represents agroup having 1-6 carbon atoms.

[0034] “Aromatic group” represents a 6-membered monocyclic aromaticgroup or condensed ring group consisting of up to 4 of 6-memberedaromatic rings.

[0035] “Heterocyclic group having conjugated double bonds” represents a5- or 6-membered mono-cyclic group or condensed ring group having atleast one hetero-atom selected from N, S and O and conjugated doublebonds. When it represents a condensed ring group, said group may have upto 6 rings.

[0036] In the present invention “dimerization” or “dimerizing” of amonohydroxy aromatic acid means forming a single bond between thearomatic rings at any position of the two-molecules by means ofoxidation coupling reaction. The dimeric composition obtained by saidreaction is recited as “dimer”.

[0037] According to the present invention, examples of preferablydimerized monohydroxy aromatic compounds include phenol, naphthol andderivatives thereof.

[0038] The position of the bonding may differ among the compounds andfor example, phenols or its derivatives bind at their o- or p-positions(Scheme 1).

[0039] α-naphthols and derivatives thereof bind at 2-positions of thenaphthalene rings (scheme 2) and β-naphthols and derivatives thereofbind at their 1 or 3 positions (scheme 3).

[0040] Further, after the single bonding is formed, some dimers ofphenol derivatives and naphthol derivatives are further oxidized to givedimers wherein two monohydroxy aromatic compound molecules are bound bya double bond (schemes 4 and 5).

[0041] The instant invention also cover the dimers as above, which aredimerized by a double bond.

[0042] Especially preferable monohydroxy aromatic compound dimerized bythe instant method is a compound represented by formula [II]:

[0043] wherein Y₁ and Y₂ may be same or different and each is selectedfrom the group consisting of hydrogen atom, an esterified carboxylgroup, a group of —(CONH)n-X (wherein X is an optionally branched andoptionally substituted hydrocarbon group which may have an unsaturatedbond, an optionally substituted aromatic group or a heterocyclic grouphaving conjugated double bonds, n is an integer of 1 or 2);

[0044] Q is selected from the group consisting of an optionally branchedalkyl and alkoxy group of 1-6 carbon atoms, halogen atom, nitro group ornitroso group; and

[0045] m represents an integer of 0-3.

[0046] Examples of preferred esterified carboxyl groups of Y₁ and Y₂ mayinclude alkoxycarbonyl group of 1-6 carbon atoms, such asmethoxycarbonyl, ethoxycarbonyl, propyloxycarbonyl,isopropyloxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl,pentyloxycarbonyl and hexyloxycarbonyl groups, phenoxy carbonyl groupand phenacyloxycarbonyl group. In case the group has an aromatic moiety,said moiety may have a substituent.

[0047] Examples of the optionally branched and optionally substitutedhydrocarbon group which may have an unsaturated bond of X may includealkyl of 1-20 carbon atoms such as ethyl, butyl, octyl, dodecyl andoctadecyl, alkenyl of 2-6 carbon atoms such as vinyl, allyl andpentenyl. Examples of the optionally substituted aromatic group of X mayinclude, for example, phenyl, naphthyl, anthryl, anthraquinonyl andpyrenyl. Examples of the optionally substituted heterocyclic grouphaving conjugated double bonds of X may include, for example, thiofuryland furyl.

[0048] Examples of substituents in each definition may include thoseexplained as substituents for Ar of formula [I].

[0049] In the present invention, the naphthalene ring of the formula[II] compound may have substituents of Q. The optional substituent Q mayrepresent an optionally branched alkyl or alkoxy group of 1-6 carbonatoms, halogen atom, nitro or nitroso group.

[0050] The number of the substituent of m is usually 0 and may be up to3.

[0051] The compound represented by formula [II], which is especiallyuseful for the method of the instant invention, may be obtained by thefollowing method:

[0052] Firstly, 2-hydroxynaphthalene-3,6-dicarboxylic acid may beobtained by the process according to WO98/17621 (Japanese patentApplication No. 10-519205), that is, by reacting potassium 2-naphtholateand carbon dioxide, aciding out the reaction to obtain the compound and,if desired, purifying the same.

[0053] Then, an acid chloride of thus obtained2-hydroxynaphthalene-3,6-dicarboxylic acid may be prepared by reactingwith thionyl chloride or the like in a solvent such as xylene,tetrahydrofuran and sulfolane in a conventional manner, and then, may betreated with an amine to give the amide compound. Alternatively,2-hydroxynaphthalene-3,6-dicarboxylic acid may be reacted directly withan amine in the presence of phosphorus trichloride ordicyclohexylcarbodiimide to give the amide compound.

[0054] An ester compound of formula [I] may be obtained by aconventional method, for example, by heating2-hydroxynaphthalene-3,6-dicarboxylic acid in an alcohol in the presenceof an acid catalyst.

[0055] Further, a compound of formula [I] wherein one of thesubstituents at 3- and 6-positions is an ester and the other is an amidemay be obtained from 2-hydroxynaphthalene-3,6-dicarboxylic acid by meansof the method described in WO96/32366. That is, condensation reaction ofthe naphthol derivative, 2-hydroxynaphthalene-3,6-dicarboxylic acid 3-or 6-mono ester and an aniline compound may be carried out. After that,water may be added thereto and then the reaction mixture may beneutralized and filtrated to give the desired compound.

BRIEF DESCRIPTION OF THE DRAWINGS

[0056]FIG. 1 is an infrared absorption spectrum (KBr) of the dimerobtained in Example 1.

[0057]FIG. 2 is an infrared absorption spectrum (KBr) of the dimerobtained in Example 2.

[0058] The present invention is further described in reference to thefollowing examples. The following examples are intended to illustratethe invention and are not to be construed to limit the scope of theinvention.

EXAMPLE 1

[0059]

[0060] 10.3 g of 2,6-di-t-butylphenol was dissolved in 100 g ofN,N-dimethylformamide, 0.5 g of copper(I) chloride was added thereto andstirred at 60° C. The solution was heated for about 10 hours under airbubbling. The precipitates were collected by filtration, washed wellwith water and methanol and dried to give 9.6 g of brown crystal(decomposition point:. 248° C., MS m/z 408 (MW=408.6)).

[0061] The infrared absorption spectrum (KBr) of the dimer is shown inFIG. 1.

EXAMPLE 2

[0062]

[0063] 10.1 g of 2-hydroxy-3-methoxycarbonyl naphthalene was dissolvedin 150 g of N,N-dimethylformamide, 0.5 g of copper(I) chloride was addedthereto and stirred at 70° C. The solution was heated for about 18 hoursunder air bubbling. The reaction mixture was then poured into 500 g ofwater and the precipitates were collected by filtration. Theprecipitates were washed well with water and methanol and dried to give9.4 g of yellow powder (melting point: 146° C., decomposition point:339° C., MS: m/z 401(MW=402.4)).

[0064] The infrared absorption spectrum (KBr) of the dimer is shown inFIG. 2.

EXAMPLES 3-21

[0065] According to the same manner as described in Example 2 with theexception that phenol and naphthol derivatives shown in table 1 wereused instead of 2-hydroxy-3-methoxycarbonylnaphthalene, dimers shown intable 1 were prepared. Mass spectroscopy data of the respective dimersare shown in table 1. TABLE 1 Ex. No. phenol/naphthol dimer MS 3

m/z 408 4

m/z 284 5

m/z 286 6

m/z 508 7

m/z 486 8

m/z 458 9

m/z 517 10

m/z 761 11

m/z 943 12

m/z 974 13

m/z 724 14

m/z 823 15

m/z 861 16

m/z 1002 17

m/z 822 18

m/z 918 19

m/z 869 20

m/z 1016 21

m/z 1258

[0066] Industrial applicability

[0067] Dimers of the monohydroxy aromatic compound obtained by thepresent invention are useful for manufacturing antiseptic compounds ortoning agents. According to the method of the present invention, dimerof a monohydroxy aromatic acid compound can be prepared in high yieldwith low cost.

1. A method for preparing dimer of a monohydroxy aromatic compoundrepresented by formula [I]: Ar—OH   [I] wherein Ar represents anoptionally substituted aromatic group characterized in that carrying outoxidative coupling reaction of the monohydroxy aromatic compound in anitrogen containing polar solvent in the presence of a copper salt. 2.The method of claim 1, wherein the monohydroxy aromatic compound isselected from the group consisting of phenol, naphthol and derivativesthereof.
 3. The method of claim 1, wherein the monohydroxy aromaticcompound is a compound represented by formula [II]:

wherein Y₁ and Y₂ may be same or different and each is selected from thegroup consisting of hydrogen atom, an esterified carboxyl group, a groupof —(CONH)n-X (wherein X is an optionally branched and optionallysubstituted hydrocarbon group which may have an unsaturated bond, anoptionally substituted aromatic group or a heterocyclic group havingconjugated double bonds, n is an integer of 1 or 2); Q is selected fromthe group consisting of an optionally branched alkyl and alkoxy group of1-6 carbon atoms, halogen atom, nitro group or nitroso group; and mrepresents an integer of 0-3.
 4. The method of claim 1, wherein thecopper salt is copper(I) chloride.
 5. The method of claim 1, wherein theoxidative coupling reaction is carried out in the presence of oxygen. 6.The method of claim 1, wherein the nitrogen containing polar solvent isselected from the group consisting of formulae [III] and [IV]:

wherein R₁, R₂, R₃ and R₄ may be same or different and each is selectedfrom the group consisting of formyl, alkyl, alkenyl, acyl and optionallysubstituted phenyl groups.
 7. The method of claim 1, wherein thenitrogen containing polar solvent is selected from the group consistingof N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone,morpholine, N-methylmorpholine, N,N-diethylacetamide,N,N-dimethylpropyoamide, tetramethyl urea, tetraethylurea,N-methylacetanilide, N,N-dimethyl aniline, N,N-dimethylanisidine,pyridine, and 2-methyl pyridine.
 8. The method of claim 1, wherein thenitrogen containing polar solvent is selected from the group consistingof N,N-dimethylformamide, N,N-dimethylacetaminde andN-methyl-2-pyrrolidone.